There is a developing consensus that environmental stimuli associated with the drug-taking experience can acquire the capacity to energize drug craving, seeking and consumption. The PI has developed a "stimulus-compounding" model of drug abuse that elucidates how multiple drug-associated stimuli interact to motivate drug-related behavior. Research stimulated by this model has revealed that simply exposing rats to certain combinations of drug-related cues can override the mechanisms that normally regulate drug-intake, causing them to double their intake of cocaine or heroin and triple their rates of drug seeking. The human drug abuse environment is rife with cues that could have analogous effects. Thus, environmentally induced enhancement of drug intake may be one factor responsible for the spiraling escalation and "uncontrollability" of drug use often seen in addicted individuals. In the proposed research, we will continue to investigate the excitatory conditions that determine how long this escalation is sustained. However, the proposed research will primarily explore methods by which drug taking can be reduced. Conditioned inhibitors are stimuli that signal drug absence and may thereby attenuate or even eliminate the incentive motivation that chives drug-related behavior. The systematic investigation of conditioned inhibition within the context of drug self-administration will be the major new objective of this program and should provide information relevant to the treatment of drug abuse. Strategies will be compared to determine the most effective means of counteracting a history of excitatory drug-related conditioning. When the program is completed, we should have a better understanding of: (1) how conditioned inhibitors can attenuate the motivation to abuse drugs, (2) how the motivational effects of multiple drug-related stimuli might lead to persistent, uncontrollable escalation of drug use, and (3) how drug and non-drug reinforcement processes are related.